Immune therapies in pancreatic ductal adenocarcinoma: Where are we now?

被引：95

作者：

Hilmi, Marc ^{[1
]}

Bartholin, Laurent ^{[2
]}

Neuzillet, Cindy ^{[1
]}

机构：

[1] Univ Paris Est Creteil, Hop Henri Mondor, AP HP, Serv Oncol Med, 51 Ave Marechal de Lattre de Tassigny, F-94010 Creteil, France

[2] Univ Claude Bernard Lyon 1, Univ Lyon, INSERM,U1052, CNRS 5286,Ctr Leon Berard,Ctr Rech Cancerol Lyon, F-69008 Lyon, France

来源：

WORLD JOURNAL OF GASTROENTEROLOGY | 2018年 / 24卷 / 20期

关键词：

Drug therapy combination; Immunology; Hypoxia; Checkpoint inhibitor; Inflammation; Pancreatic cancer; Tumor-infiltrating lymphocyte; Transforming growth factor beta; Tumor microenvironment; COLONY-STIMULATING FACTOR; EXPRESSING MESOTHELIN CRS-207; ALGENPANTUCEL-L IMMUNOTHERAPY; STANDARD ADJUVANT THERAPY; RAS PEPTIDE VACCINATION; SECRETING TUMOR VACCINE; T-CELL INFILTRATION; PD-1; BLOCKADE; PHASE-I; CANCER-IMMUNOTHERAPY;

D O I：

10.3748/wjg.v24.i20.2137

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, mostly due to its resistance to treatment. Of these, checkpoint inhibitors (CPI) are inefficient when used as monotherapy, except in the case of a rare subset of tumors harboring microsatellite instability (< 2%). This inefficacy mainly resides in the low immunogenicity and non-inflamed phenotype of PDAC. The abundant stroma generates a hypoxic microenvironment and drives the recruitment of immunosuppressive cells through cancerassociated- fibroblast activation and transforming growth factor beta secretion. Several strategies have recently been developed to overcome this immunosuppressive microenvironment. Combination therapies involving CPI aim at increasing tumor immunogenicity and promoting the recruitment and activation of effector T cells. Ongoing studies are therefore exploring the association of CPI with vaccines, oncolytic viruses, MEK inhibitors, cytokine inhibitors, and hypoxia-and stroma-targeting agents. Adoptive T-cell transfer is also under investigation. Moreover, translational studies on tumor tissue and blood, prior to and during treatment may lead to the identification of biomarkers with predictive value for both clinical outcome and response to immunotherapy.

引用

页码：2137 / 2151

页数：15

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